联合降压药物治疗要点及其药物选择-钙拮抗剂的价值

1、联合降压药物治疗要点及其药物选择-钙拮抗剂的价值P for heterogeneity = 0.002澳洲亚洲Hazard ratio+10 mmHg: 1.22 (1.18-1.26)+10 mmHg: 1.31 (1.26-1.35)Mean usual SBP (mmHgl)收缩压与冠心病事件收缩压与致死及非致死缺血性卒中P for heterogeneity = 0.001澳洲亚洲+10 mmHg: 1.24 (1.15-1.35)+10 mmHg: 1.53 (1.48-1.59) Hazard ratioMean usual SBP (mmHgl) 1101201301401501

2、60170 1101201301401501601700.51.02.04.08.00.51.02.04.08.00306090120150198519901995200020052010 (年)脑血管病冠心病标化死亡率(1/10万)CV死亡率呈上升趋势CHD为第二位CV死因冠心病: 中国人群死亡重要原因在中国，高血压是冠心病的重要危险因素高血压导致心血管病的相对危险高达3-4倍在总的CV事件中，23.7%的急性冠心病事件归因于高血压CHD死亡48%中国心血管病报告20052004年城市居民CHD死亡占所有心脏病死亡的48%Stroke and MI in Hypertension Trial

3、s1. Kjeldsen SE et al. Blood Pressure 2001;10:190-192. 2. Dalhf B et al. Lancet 2002;359:995-1003. 3. Wing LMH et al. N Engl J Med 2003;348:583-592. 5012345678STOP-1SHEPSTONESYST-EURSYST-CHINAHOTCAPPPSTOP-2NICSNORDILINSIGHTPercentage of patients with eventStrokeMyocardial InfarctionPercentage of fat

4、al and nonfatal strokes, and fatal and nonfatal MIs reported in large, prospective hypertension trials published after 1990.LIFEANBP2高血压患者脑卒中/心肌梗死发病率STONE8.0Syst-China8.7NICS-EH4.0SHEP1.2MRC II0.8STOP-II1.2Syst-Eur1.7抗高血压治疗效果%降低MacMahon SW et al. Prog Cardiovasc Dis. 1986;29(suppl 1):99118.605040302

5、010048%16%脑血管疾病冠心病不同年龄的缺血性心脏病风险与血压关系Lewington et al. Lancet. 2002;360:1903-1913.40-49 years50-59 years60-69 years70-79 years80-89 years收缩压Age at risk:IHD Mortality(Floating Absolute Risk and 95% CI)2561286432168421120140160180Usual SBP (mm Hg)舒张压IHD Mortality(Floating Absolute Risk and 95% CI)256128

6、6432168421708090100110Usual DBP (mm Hg)Age at risk:40-49 years50-59 years60-69 years70-79 years80-89 yearsLower Is Better 至少将血压降至 SBP 140mmHg 和 DBP 90mmHg 对糖尿病患者 SBP 130mmHg 和 DBP 80mmHg 对老年人SBP 150mmHg和 DBP 90mmHg 仍然强调严格控制血压降压治疗的目标中国高血压指南2004高血压药物治疗的目的 减少总的心血管病死率和病残率，而不仅仅是降低血压抗高血压治疗的策略降压达标是手段，靶器官保护

7、是关键治疗后血压水平与冠心病进展Sipahi I, et al. JACC Vol. 48, No. 4, 2006BP Differences of 2 mmHg Are Associated With Up to a 40% Effect on CV Risk Meta-analysis of 61 prospective, observational studies1 million adults12.7 million person-years Lewington S et al. Lancet. 2002;360:19031913.2 mmHg decrease in mean SB

8、P10% reduction in risk of stroke mortality7% reduction in risk of IHD mortality2007ESH-ESC：及时启动药物治疗启动药物治疗启动药物治疗启动药物治疗Target BP (mm Hg)Number of antihypertensive agents1Trial234AASKMAP 92UKPDSDBP 85ABCDDBP 75MDRDMAP 92HOTDBP 80IDNTSBP 135/DBP 85ALLHATSBP 140/DBP 90Multiple Antihypertensive Agents Are

9、 Needed to Achieve Target BPDBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure. Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.Lewis EJ et al. N Engl J Med. 2001;345:851-860.Cushman WC et al. J Clin Hypertens. 2002;4:393-405.2007ESH-ESC：联合治疗成为最重要的治疗策略为了达到降压目标

10、，大部分高血压患者需要使用一种以上的降压药物。联合治疗被推荐可作为起始治疗，特别是2级或3级高血压患者，或总心血管风险处于高危或极高危的患者，并建议更快地调整剂量，以使病人尽快达到目标血压。治疗高血压首先必须降压达标降压达标的必然选择联合抗高血压药物治疗钙拮抗剂的临床意义2007 ESH-ESC 高血压诊治指南2007-06-12利尿剂 受体阻断剂 受体阻断剂ACE抑制剂钙拮抗剂血管紧张素受体阻断剂(ARBs)HOT研究治疗方案 *治疗二周目标血压DBP仍大于90mmHg第一步第二步第三步第四步第五步波依定 5mg波依定 5mg + 25mg 倍他乐克/低剂量ACEI波依定 10mg + 25

11、mg 倍他乐克/低剂量ACEI波依定 10mg + 50mg 倍他乐克/高剂量ACEI波依定 10mg + 50mg 倍他乐克/高剂量ACEI+低剂量其他降压药(受体阻滞剂/ACE抑制剂)/利尿剂*HOT Study Group. Lancet. 1998;351:1755-1762.亚洲人群使用波依定血压达标率更高 (Target 90mmHg)89%97%98%舒张压 (mmHg)97%95%97%74%80%85%83%86%86%随访(月)080859095100105036122436终点全球亚洲p0.001p0.05p0.01p0.05nsnsnsnsnsnsp0.01*发生副作用

12、的病人%随访时间全球病人亚洲病人010.817.13.06.22.53.23.94.34.97.00.61.61.16.502.66.21.13.78.50246810121416183M6M12M18M24M30M36M42M48M54MFinal9.0亚洲人群使用波依定副作用更少 钙拮抗剂特有的全面作用血管平滑肌的刺激与收缩机理血管平滑肌血管平滑肌收缩细胞内信息传导途径钙拮抗剂治疗高血压的长处老年和低肾素活性患者有较好降压疗效高钠摄入不影响降压疗效非甾体类抗炎症药物不干扰降压作用在嗜酒的患者有显著降压作用适用于合并糖尿病、冠心病或外周血管病患者抗动脉粥样硬化作用降压药物强制和可能的禁忌症绝

13、对禁忌症相对禁忌症噻嗪类利尿剂痛风代谢综合征、糖耐量异常、妊娠受体阻滞剂哮喘房室传导阻滞（2或3度） 外周动脉疾病、代谢综合征、糖耐量异常、慢性阻塞性肺病、运动员或经常锻炼的患者 钙拮抗剂（双氢吡啶类）快速性心律失常、心力衰竭钙拮抗剂（维拉帕米/地尔硫卓）房室传导阻滞（2或3度）心力衰竭血管紧张素转换酶抑制剂妊娠、血管神经性水肿、高钾血症、双侧肾动脉狭窄血管紧张素受体拮抗剂妊娠、高钾血症、双侧肾动脉狭窄利尿剂（抗醛固酮剂）肾功能衰竭、高钾血症与其他降压药物相比，二氢吡啶类钙拮抗剂没有任何绝对禁忌证，是临床使用中最安全的一类降压药物 联合降压治疗的药物选择Paolo Verdecchia,et

14、al.Hypertension 2005;46;386-392降压药物预防脑卒中事件随机组间收缩压的差值（mmHg）CAPPPPEACEPROGRESSPROGRESSComCAMELOTEUROPAHOPEANBP2STOP2/ACE-IALLHAT/ACE-IIDNT2CAMELOTSyst-ChinaSYST-EURSTONEPREVENTCONVINCEMIDASINSIGHTNORDILSTOP2/CCBALLHAT/CCBINVESTNORDILSHELL.2.4.6.811.21.42.01.8-5051015-5051015ELISA卒中事件ORACEICCBPART-2LIK

15、PDS39SCATNICOLEACTIONNICSVHAS B.Dahlof (Co-chair), P.Sever (Co-chair), N. Poulter (Secretary) H. Wedel (Statistician), G. Beevers, M. Caulfield, R. CollinsS. Kjeldsen, A. Kristinsson, J. Mehlsen, G. McInnes, M. Nieminen E. OBrien, J. stergren, on behalf of the ASCOT InvestigatorsA randomised control

16、led trial of the prevention of CHD and other vascular events by BP and cholesterol lowering in a factorial study designSystolic and diastolic blood pressuremm Hg6080100120140160180Time (years)Baseline0.511.522.533.544.555.5 atenolol thiazide amlodipine perindopril137.7136.179.277.4Mean difference 1.

17、9Last visitMean difference 2.7SBPDBP163.9164.194.894.586% pts on combination therapiesAll-cause mortality Number at riskAmlodipine perindopril 96399544 9441 93329167 8078Atenolol thiazide 96189532 9415 92619085 79750.01.02.03.04.05.0Years0.02.04.06.08.010.0HR = 0.89 (0.810.99)p = 0.0247%Amlodipine p

18、erindopril(No. of events 738)Atenolol thiazide(No. of events 820)CV death + MI + stroke0.01.02.03.04.05.0Years0.00.02.04.06.08.010.0Amlodipine perindopril(No. of events = 796)Atenolol thiazide(No. of events = 937)HR = 0.840 (0.760.92)p 0.0003Number at riskAmlodipine perindopril 96399415 9228 9007877

19、8 7655Atenolol thiazide 96189400 9152 88918629 7500%Avoiding Cardiovascular Events throughCOMbination Therapy in Patients LIving with Systolic HypertensionKenneth Jamerson1, George L. Bakris2, Bjorn Dahlof3, Bertram Pitt1, Eric J. Velazquez4, and Michael A. Weber5 for the ACCOMPLISH InvestigatorsUni

20、versity of Michigan Health System, Ann Arbor, MI1; University of Chicago-Pritzker School of Medicine, Chicago, IL2; Sahlgrenska University Hospital, Gothenburg, Sweden3; Duke University School of Medicine, Durham, NC4; SUNY Downstate Medical College, Brooklyn, NY5 2008.04.01 57th ACCACCOMPLISH: Desi

21、gnJamerson KA et al. Am J Hypertens. 2003;16(part2)193A*Beta blockers; alpha blockers; clonidine; (loop diuretics).14 DaysDay 1Month 1Month 2Year 5ScreeningAmlodipine 5 mg +benazepril 20 mgRandomizationBenazepril 40 mg + HCTZ 12.5 mgBenazepril 40 mg + HCTZ 25 mgFree add-on antihypertensive agents*Mo

22、nth 3Free add-on antihypertensive agents*Amlodipine 5 mg +benazepril 40 mgAmlodipine 10 +benazepril 40 mgBenazepril 20 mg + HCTZ 12.5 mgTitrated to achieve BP140/90 mmHg; 130/80 mmHg in patients with diabetes or renal insufficiencySystolic Blood Pressure Over Timemm HgMonth57315387520649994804428525

23、20104557095377515449804831428625941075PatientsACEI / HCTZN=5733CCB / ACEIN=5713*Mean values are taken at 30 months F/U visit129.3 mmHg130mmHgDifference of 0.7 mmHg p0.05*DBP: 71.1DBP: 72.8Baseline Control Rates37.237.9ACCOMPLISH: Exceptional Control Rates with Initial Combination TherapyACEI / HCTZN

24、=5733Control rate (%)CCB / ACEIN=571310203040506070809078.581.7P0.001 at 30 months follow-up Control defined as 140/90 mmHgKaplan Meier for Primary EndpointCumulative event rateHR (95% CI): 0.80 (0.72, 0.90)20% Risk ReductionTime to 1st CV morbidity/mortality (days)p = 0ACEI / HCTZCCB / ACEI650526.0

25、002INTERIM RESULTS Mar 08Primary and Other EndpointsComposite CV mortality/morbidityPrimary w/o revascularizationHard CV endpoint(CV death, non-fatal MI, non-fatal stroke)All cause mortalityIncidence of adjudicated primary endpoints, based upon cut-off analysis date 3/24/2008(Intent-to-treat populat

26、ion)Risk Ratio(95%)0.80 (0.720.90)0.79 (0.680.92)0.80 (0.680.94)0.90 (0.751.08) 0.51.02.0Favors CCB / ACEIFavors ACEI / HCTZINTERIM RESULTS Mar 08降低脑卒中危险,络活喜显著优于其他降压药物40%18%16%14%P=0.038P=0.004P=0.032P=0.002VS.安慰剂VS.ACEIVS.ARB VS.利尿剂/受体阻滞剂荟萃分析:PREVENT(n=825)/CAMELOT(n=1318)/IDNT(n=1136)脑卒中发生危险降低(%)荟

27、萃分析:ALLHAT(n=18102)/CAMELOT(n=1336)荟萃分析:IDNT(n=1146)/VALUE(n=15245)荟萃分析:ALLHAT(n=24309)/ASCOT(n=19257)Franz H. Messerli et al. Hypertension. 2006;48:359-361.降低冠心病事件,络活喜和ACEI类似31%18%4%1%P=0.031P=0.009P=0.26P=0.89VS.安慰剂VS.ACEIVS.ARBVS.利尿剂/受体阻滞剂荟萃分析:PREVENT(n=825)/CAMELOT(n=1318)/IDNT(n=1136)冠心病事件发生发生危

28、险降低(%)荟萃分析:IDNT(n=1146)/ VALUE(n=15245)荟萃分析:ALLHAT(n=18102)/CAMELOT(n=1336)荟萃分析:ALLHAT(n=18102)/CAMELOT(n=1336)Franz H. Messerli et al. Hypertension. 2006;48:359-361.ACTIONNORDILINSIGHTSTOP-2-ASTOP-2-CALLHAT-AALLHAT-DINVESTCONVINCEASCOTVALUESyst-EurSyst-ChinaIDNT-pboIDNT-IrbeCCB与对照药物收缩压差值 (mm Hg)-5 0 5 10 15 0.500.751.001.251.50氨氯地平的临床研究均符合降低血压减少冠心病事件的规律William J. Elliott et al. Circulation 2006;113:2763-2772ACTION:降压